The brain is critically dependent on the circulating blood for a supply of essential amino acids for both protein and neurotransmitter synthesis. The rate-limiting step to entry appears to be passage across the blood-brain barrier catalyzed by saturable processes which have distinct kinetic parameters for neutral, basic and acidic amino acids. The blood-brain barrier transport systems are in a unique position to regulate amino acid entry and thereby affect brain function. It has been established that during at least two pathological conditions, hepatic encephalopathy and hypothyroidism, the transport of the different classes of amino acids is altered in a characteristic way. To date, virtually all studies examining blood-brain barrier transport have been conducted in whole brain. However, further advances in our knowledge of brain function require the understanding of these processes at the structural level. It is the purpose of this proposal to move on to the study of local transport, i.e., at the level of the individual brain structures using an autoradiographic technique developed in the principal investigator's laboratory. The primary effort will be to study the distribution of the three amino acid transport systems in normal rats using representative amino acids of each class. On completion of this phase, amino acid transport in pathological conditions will be examined to determine the location of changes in the blood-brain barrier and their possible relevance to the disease process.